EP2865391B1 - Verfahren zur Herstellung einer gefriergetrockneten pharmazeutischen Zusammensetzung mit Gehalt an Mitomycin C - Google Patents

Verfahren zur Herstellung einer gefriergetrockneten pharmazeutischen Zusammensetzung mit Gehalt an Mitomycin C Download PDF

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Publication number
EP2865391B1
EP2865391B1 EP13189775.3A EP13189775A EP2865391B1 EP 2865391 B1 EP2865391 B1 EP 2865391B1 EP 13189775 A EP13189775 A EP 13189775A EP 2865391 B1 EP2865391 B1 EP 2865391B1
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European Patent Office
Prior art keywords
mitomycin
solution
butanol
tert
solutions
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EP13189775.3A
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German (de)
English (en)
French (fr)
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EP2865391A1 (de
Inventor
Sonja Schuldt-Lieb
Sebastian Bialleck
Ingo Guhde
Michaela Rehberg
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Medac Gesellschaft fuer Klinische Spezialpraeparate mbH
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Medac Gesellschaft fuer Klinische Spezialpraeparate mbH
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Priority to LTEP17188743.3T priority Critical patent/LT3272361T/lt
Priority to PL13189775T priority patent/PL2865391T3/pl
Priority to NO13189775A priority patent/NO2865391T3/no
Priority to DK17188743.3T priority patent/DK3272361T3/da
Priority to PT171887433T priority patent/PT3272361T/pt
Priority to PL17188743T priority patent/PL3272361T3/pl
Priority to ES17188743T priority patent/ES2771227T3/es
Priority to EP17188743.3A priority patent/EP3272361B1/de
Priority to PT131897753T priority patent/PT2865391T/pt
Priority to ES13189775.3T priority patent/ES2648367T3/es
Priority to EP13189775.3A priority patent/EP2865391B1/de
Priority to DK13189775.3T priority patent/DK2865391T3/da
Priority to LTEP13189775.3T priority patent/LT2865391T/lt
Application filed by Medac Gesellschaft fuer Klinische Spezialpraeparate mbH filed Critical Medac Gesellschaft fuer Klinische Spezialpraeparate mbH
Priority to JP2016525064A priority patent/JP6461945B2/ja
Priority to US15/031,519 priority patent/US10688049B2/en
Priority to CN201480057080.2A priority patent/CN105744957B/zh
Priority to PCT/EP2014/072201 priority patent/WO2015059023A1/de
Priority to EA201690793A priority patent/EA036982B1/ru
Publication of EP2865391A1 publication Critical patent/EP2865391A1/de
Priority to HK15108977.3A priority patent/HK1208351A1/xx
Publication of EP2865391B1 publication Critical patent/EP2865391B1/de
Application granted granted Critical
Priority to JP2018242147A priority patent/JP6869941B2/ja
Priority to US16/876,505 priority patent/US11766405B2/en
Active legal-status Critical Current
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia

Definitions

  • the invention relates to a process for the preparation of a freeze-dried pharmaceutical composition containing mitomycin C, which is characterized by a high stability and purity and can be quickly reconstituted into ready-to-use solutions.
  • the GB 2171408 describes the lyophilization of mitomycin derivatives with tert-butanol.
  • the US 5,216,011 describes solutions of mitomycin C, which can be administered by injection, for example. These solutions are intended to circumvent difficulties in the production of freeze-dried preparations.
  • the solutions contain as solvent 40 to 100 vol .-% of propylene glycol and 0 to 60 vol .-% water.
  • aqueous solution of mitomycin C which contains buffers and has a pH in the range of 6.0 to 9.0.
  • the solution is characterized by a specific ratio of concentration of mitomycin C to ionic strength of the buffer.
  • the invention likewise provides the freeze-dried pharmaceutical composition according to claims 8 to 12 and the mitomycin C-containing solution according to claim 13.
  • the process according to the invention for the preparation of a freeze-dried pharmaceutical composition containing mitomycin C is characterized in that a solution of mitomycin C is freeze-dried, the solution containing a mixture of tert-butanol and water containing 84 to 95% by weight. contains tert-butanol.
  • the mixture of tert-butanol and water used contains 88 to 92% by weight and very particularly preferably about 89% by weight of tert-butanol.
  • the solution also contains at least one adjuvant selected from the group consisting of urea, polyethylene glycol and mannitol.
  • at least one adjuvant selected from the group consisting of urea, polyethylene glycol and mannitol.
  • Lyophilisates can be prepared which have a particularly high solubility in solvents used for reconstitution. The use of these over the active ingredient inert excipients leads to a lyophilisate, which protects the drug against destabilizing influences due to its special properties and thus preserves the active ingredient in its pure form.
  • the solution may also contain other conventional auxiliaries such as other sugar alcohols, eg isomalt, lactitol, Sorbitol, lactitol, sorbitol, xylitol, threitol, erythritol or arabitol, sugars, eg sucrose, glucose, fructose, maltose, rhamnose, lactose or trehalose, amino acids, eg L-phenylalanine, L-tryptophan, L-proline, L-histidine, L-glycine or L-arginine, polymers, for example polyvinylpyrrolidones, polyvinyl acetates, starch derivatives, eg cyclodextrins, dextroses, amylopectins, amyloses, polysaccharides, eg alginates, pectins, celluloses, agents for terminating isotonicity, for example sodium chlor
  • the freeze-drying of the lyophilization solution is generally carried out using lyophilization processes and equipment commonly used for pharmaceutical purposes.
  • the solution is filled into a suitable vessel, and the vessel is placed in a conventional freeze dryer with coolable and heatable shelves on which the solution can be exposed to the various temperatures of the freeze-drying process.
  • the solution is usually frozen and exposed to a reduced atmospheric pressure. This leads to a high degree to the sublimation of solvent from the frozen solution, which is reflected, for example, in designated cooler areas of the freeze dryer. This is followed by regular secondary drying at higher temperatures.
  • the lyophilizate obtained is usually allowed to come to room temperature and closes the used vessel under sterile conditions.
  • a suitable program for lyophilization may include loading the vessel at room temperature, freezing at -50 ° C to -35 ° C at normal pressure, then lowering the atmospheric pressure and then raising the temperature by 25 to 95 ° C to effect drying.
  • the invention is also directed to a freeze-dried pharmaceutical composition containing mitomycin C, wherein the Composition is obtainable by the method according to the invention.
  • composition according to the invention preferably contains at least one adjuvant selected from the group consisting of urea, polyethylene glycol and mannitol.
  • adjuvant selected from the group consisting of urea, polyethylene glycol and mannitol.
  • the composition usually contains urea in a concentration of 0.2 to 1, in particular 0.5 to 0.99, preferably 0.8 to 0.95 and particularly preferably 0.93 to 0.94 g per gram of composition.
  • the composition usually contains polyethylene glycol in a concentration of 0.2 to 1, in particular 0.5 to 0.99, preferably 0.8 to 0.95 and particularly preferably 0.93 to 0.94 g per gram of composition.
  • composition according to the invention contains the impurities D1, D2 and albomitomycin C in a total amount of in particular less than 2.0%, preferably less than 1.5%, more preferably less than 1.0%, more preferably less than 0.8% and most preferably less than 0.6%, wherein the amount of these impurities is determined according to the impurity method according to Ph Eur 8.0 Mitomycin Monograph 01/2008: 1655. This method of determination is also referred to as method 4 in the examples.
  • solutions were prepared using these solvents, respectively, for No. 6 (DMSO / DMAA) 0.53 mg / g mitomycin C and 8.0 mg / g urea and for No. 7 (DMSO) 1.82 mg / g mitomycin C and 27.3 mg / g urea.
  • DMSO DMSO
  • the solutions were stored at room temperature and with exclusion of light for a period of up to 71.5 hours.
  • Mitomycin C proved to be very stable in both solvents.
  • the use of DMSO alone resulted in a particularly low decrease of the original content of mitomycin C from 100% to 99.32% over a period of 26.5 hours.
  • Method 3 corresponds to the content method according to Ph Eur 8.0 Mitomycin Monograph 01/2008: 1655.
  • Method 4 corresponds to the impurity method according to Ph Eur 8.0 Mitomycin Monograph 01/2008: 1655.
  • solutions were prepared using these mixtures, their concentrations of mitomycin C 2.1 mg / g for mixture no. 8, 2.2 mg / g for mixture no. 9 and 2.4 mg / g for mixture no 10 was.
  • mitomycin C was added in an amount to obtain a solution having a concentration of 5 mg / g of mitomycin C.
  • a mitomycin-containing solution in pure tert-butanol (100 wt%) (# 14) and a solution in water (# 15) were prepared for comparison. In the experiment with pure tert-butanol, this was first melted by heating to about 30 ° C and then the mitomycin C dissolved in the melt.
  • a particularly high purity of 100.0% by weight after 24 hours was achieved in 100% by weight of tert-butanol, but the solubility of mitomycin C in pure tert-butanol is lower.
  • urea was dissolved in an amount to obtain a concentration of 5% by weight. Then, mitomycin C was added in an amount to give a concentration of 3.33 mg / g, and the solution was stirred for one hour. The solution was filled into brown glasses and stored for 9 days at room temperature (RT) without light protection, at room temperature (RT) with the exclusion of light and at 5 ° C with the exclusion of light.
  • Lyophilisates were obtained by conventional freeze-drying with (i) freezing the solutions, (ii) applying a vacuum, (iii) primary and (iv) secondary drying. These were reconstituted with water and the reconstituted solutions obtained were analyzed for their content of mitomycin C as well as impurities according to Example 1. The results are shown in Table 12. ⁇ b> Table 12 "Content of mitomycin C and impurities after freeze-drying and reconstitution" ⁇ /b> Amount of tert.
  • Example 7 Stability of mitomycin C in tert-butanol-water mixture (89/11) with 20 mg / g urea
  • the purity of the solution is surprisingly high, reflecting the surprisingly high stability of the active ingredient in the solvent.
  • the purity of the solution is surprisingly high, reflecting the surprisingly high stability of the active ingredient in the solvent.
  • Solutions of mitomycin C were prepared in a mixture of 89% by weight of tert-butanol and 11% by weight of water. In addition to 3.33 mg / g mitomycin C, the solutions also contained either 50 mg / g urea or PEG 4000, respectively. Each 6 g of these solutions were filled into small vials and freeze-dried in a conventional manner. The cakes of the lyophilizates with urea and PEG 4000 were solid and perfect.
  • the lyophilizates produced had a high purity of mitomycin C even after storage at an elevated temperature of 40 ° C, which reflects their very good stability.
  • lyophilizates could be completely reconstituted with isotonic saline in much less than 30 seconds.
  • Solutions of mitomycin C were prepared in a mixture of 89% by weight of t-butanol (TBA) and 11% by weight of water. The solutions contained, in addition to 1.33 mg / g mitomycin C also each 20 mg / g urea. Each 1.5 g of this solution were filled into small vials and freeze-dried in a conventional manner. The cakes of the lyophilisates were firm and flawless.
  • TAA t-butanol
  • the lyophilizates produced had a high purity of mitomycin C, which reflects the very good stability of the active ingredient during the process.
  • lyophilizates could be completely reconstituted with isotonic saline in much less than 30 seconds.
  • Solutions of mitomycin C were prepared in a mixture of 89% by weight of t-butanol (TBA) and 11% by weight of water. The solutions contained in addition to 1.67 mg / g mitomycin C also 25 mg / g urea. Each 1.2 g of this solution were filled into small vials and freeze-dried in a conventional manner. The cakes of the lyophilisates with urea were firm and flawless.
  • TAA t-butanol
  • the lyophilizates produced had a high purity of mitomycin C, which reflects the very good stability of the active ingredient during the process.
  • the lyophilizates could be completely reconstituted with isotonic saline in much less than 30 seconds.
  • Solutions of mitomycin C were prepared in a mixture of 95% by weight of tert-butanol (TBA) and 5% by weight of water. The solutions contained in addition to 5 mg / g mitomycin C also 45 mg / g mannitol each. Each 4.0 g of this solution was filled into small vials and freeze-dried in a conventional manner. The cakes of the lyophilisates were firm and flawless.
  • TAA tert-butanol
  • the lyophilizates produced had a high purity of mitomycin C, which reflects the very good stability of the active ingredient during the process.
  • the lyophilizates could be completely reconstituted with isotonic saline in much less than 30 seconds.
  • the determination of the content of mitomycin C was carried out according to Method 3 and that of the content of impurities according to Method 4.
  • the reconstitution was carried out with 20 or 40 ml of isotonic saline solution to a final concentration of 1 mg / ml.
  • the lyophilizates produced contained even after 6 months storage at elevated temperature of 40 ° C and increased humidity of 75% RH only very small amounts of impurities.
  • Solutions of mitomycin C were prepared in a mixture of 89% by weight of tert-butanol and 11% by weight of water. The solutions also contained in addition to 3.33 mg / g mitomycin C also 50 mg / g urea. Each 6 g [equivalent to 20 mg mitomycin C] of these solutions were filled into small vials and freeze-dried in a conventional manner. The resulting lyophilizates were reconstituted with 20 ml or 10 ml of water for injection. Final concentration mitomycin C Content * mitomycin C [%] Description of the reconstituted solution 1 mg / ml 100.6 Clear, free of visible particles 2 mg / ml 100.6 Clear, free of visible particles * Determination according to method 3
  • the reconstituted solutions in water for injection had a high content of mitomycin C.
  • the solutions were clear and free of visible particles.
EP13189775.3A 2013-10-22 2013-10-22 Verfahren zur Herstellung einer gefriergetrockneten pharmazeutischen Zusammensetzung mit Gehalt an Mitomycin C Active EP2865391B1 (de)

Priority Applications (21)

Application Number Priority Date Filing Date Title
ES13189775.3T ES2648367T3 (es) 2013-10-22 2013-10-22 Procedimiento de preparación de una composición farmacéutica liofilizada que contiene mitomicina C
LTEP13189775.3T LT2865391T (lt) 2013-10-22 2013-10-22 Liofilizuotos kompozicijos, turinčios mitomiciną c, gamybos būdas
DK17188743.3T DK3272361T3 (da) 2013-10-22 2013-10-22 Fremgangsmåde til fremstilling af en frysetørret farmaceutisk sammensætning med indhold af mitomycin c
PT171887433T PT3272361T (pt) 2013-10-22 2013-10-22 Método para produzir uma composição farmacêutica liofilizada com mitomicina c
PL17188743T PL3272361T3 (pl) 2013-10-22 2013-10-22 Sposób wytwarzania suszonej przez wymrażanie kompozycji farmaceutycznej zawierającej mitomycynę C
ES17188743T ES2771227T3 (es) 2013-10-22 2013-10-22 Procedimiento de preparación de una composición farmacéutica liofilizada que contiene mitomicina C
EP17188743.3A EP3272361B1 (de) 2013-10-22 2013-10-22 Verfahren zur herstellung einer gefriergetrockneten pharmazeutischen zusammensetzung mit gehalt an mitomycin c
PT131897753T PT2865391T (pt) 2013-10-22 2013-10-22 Processo para a produção de uma composição farmacêutica liofilizada com um conteúdo de mitomicina c
PL13189775T PL2865391T3 (pl) 2013-10-22 2013-10-22 Sposób wytwarzania liofilizowanej kompozycji farmaceutycznej zawierającej mitomycynę C
EP13189775.3A EP2865391B1 (de) 2013-10-22 2013-10-22 Verfahren zur Herstellung einer gefriergetrockneten pharmazeutischen Zusammensetzung mit Gehalt an Mitomycin C
DK13189775.3T DK2865391T3 (da) 2013-10-22 2013-10-22 Fremgangsmåde til fremstilling af en frysetørret farmaceutisk sammensætning indeholdende mitomycin C
NO13189775A NO2865391T3 (da) 2013-10-22 2013-10-22
LTEP17188743.3T LT3272361T (lt) 2013-10-22 2013-10-22 Liofilizuotos farmacinės kompozicijos, kurioje yra mitomicino c, gamybos būdas
EA201690793A EA036982B1 (ru) 2013-10-22 2014-10-16 Способ получения лиофилизированной фармацевтической композиции, содержащей митомицин с
JP2016525064A JP6461945B2 (ja) 2013-10-22 2014-10-16 ある含有量のマイトマイシンｃを有する凍結乾燥医薬組成物を製造する方法
US15/031,519 US10688049B2 (en) 2013-10-22 2014-10-16 Process for the preparation of a freeze-dried pharmaceutical composition containing mitomycin C
CN201480057080.2A CN105744957B (zh) 2013-10-22 2014-10-16 制备冷冻干燥的含有丝裂霉素c的药物组合物的方法
PCT/EP2014/072201 WO2015059023A1 (de) 2013-10-22 2014-10-16 Verfahren zur herstellung einer gefriergetrockneten pharmazeutischen zusammensetzung mit gehalt an mitomycin c
HK15108977.3A HK1208351A1 (en) 2013-10-22 2015-09-14 Method for producing a freeze-dried pharmaceutical composition containing mitomycin c
JP2018242147A JP6869941B2 (ja) 2013-10-22 2018-12-26 ある含有量のマイトマイシンｃを有する凍結乾燥医薬組成物を製造する方法
US16/876,505 US11766405B2 (en) 2013-10-22 2020-05-18 Process for the preparation of a freeze-dried pharmaceutical composition containing mitomycin C

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP13189775.3A EP2865391B1 (de) 2013-10-22 2013-10-22 Verfahren zur Herstellung einer gefriergetrockneten pharmazeutischen Zusammensetzung mit Gehalt an Mitomycin C

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EP17188743.3A Division EP3272361B1 (de) 2013-10-22 2013-10-22 Verfahren zur herstellung einer gefriergetrockneten pharmazeutischen zusammensetzung mit gehalt an mitomycin c

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EP2865391A1 EP2865391A1 (de) 2015-04-29
EP2865391B1 true EP2865391B1 (de) 2017-09-20

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EP13189775.3A Active EP2865391B1 (de) 2013-10-22 2013-10-22 Verfahren zur Herstellung einer gefriergetrockneten pharmazeutischen Zusammensetzung mit Gehalt an Mitomycin C
EP17188743.3A Active EP3272361B1 (de) 2013-10-22 2013-10-22 Verfahren zur herstellung einer gefriergetrockneten pharmazeutischen zusammensetzung mit gehalt an mitomycin c

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US (2) US10688049B2 (da)
EP (2) EP2865391B1 (da)
JP (2) JP6461945B2 (da)
CN (1) CN105744957B (da)
DK (2) DK2865391T3 (da)
EA (1) EA036982B1 (da)
ES (2) ES2771227T3 (da)
HK (1) HK1208351A1 (da)
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JP6706988B2 (ja) * 2016-07-20 2020-06-10 日本化薬株式会社 ボルテゾミブを含有する医薬組成物
WO2019195386A1 (en) * 2018-04-05 2019-10-10 Tarveda Therapeutics, Inc. Pharmaceutical compositions with reduced tert-butanol levels
JP2023553976A (ja) * 2020-12-11 2023-12-26 ウロゲン ファーマ リミテッド がんを治療するための材料及び方法
CN113197870B (zh) * 2021-04-14 2022-07-01 健进制药有限公司 一种注射用丝裂霉素冻干制剂及其制备方法
WO2023042107A1 (en) * 2021-09-17 2023-03-23 Intas Pharmaceuticals Ltd. A stable ready to dilute injectable pharmaceutical formulation of mitomycin
CN114557970B (zh) * 2022-03-17 2023-03-31 浙江长典药物技术开发有限公司 一种眼用丝裂霉素冻干粉及其制备方法
WO2024079565A1 (en) * 2022-10-12 2024-04-18 Harshal Prabhakar Bhagwatwar Stable mitomycin concentrates

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EP3272361B1 (de) 2019-11-20
LT2865391T (lt) 2017-11-27
PL2865391T3 (pl) 2018-01-31
CN105744957A (zh) 2016-07-06
US11766405B2 (en) 2023-09-26
PT3272361T (pt) 2020-01-21
US20160256391A1 (en) 2016-09-08
PL3272361T3 (pl) 2020-04-30
ES2771227T3 (es) 2020-07-06
US10688049B2 (en) 2020-06-23
HK1208351A1 (en) 2016-03-04
DK3272361T3 (da) 2020-01-27
JP2016534060A (ja) 2016-11-04
JP2019043969A (ja) 2019-03-22
US20200276128A1 (en) 2020-09-03
WO2015059023A1 (de) 2015-04-30
EP2865391A1 (de) 2015-04-29
PT2865391T (pt) 2017-12-22
DK2865391T3 (da) 2017-11-20
EP3272361A1 (de) 2018-01-24
EA036982B1 (ru) 2021-01-22
JP6869941B2 (ja) 2021-05-12
ES2648367T3 (es) 2018-01-02
JP6461945B2 (ja) 2019-01-30
LT3272361T (lt) 2020-01-10
EA201690793A1 (ru) 2016-08-31
NO2865391T3 (da) 2018-02-17

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